The therapeutic effect of lithium (Li ion) in manic-depressive illness raises important unsolved questions, such as: In what ways do manic-depressives differ from normal subjects? What is the mechanism of action of Li ion? Why do some patients fail to respond to Li ion concentrations that would be effective in others? Our goals are to understand lithium distribution in the body, the cellular mechanisms underlying this distribution, and effects of lithium on the distribution of compounds possibly related causally to the mood disorders. In particular, we propose to do the following: (1) to study lithium pharmacokinetics in manic-depressive patients; (2) to measure lithium fluxes across cell membranes, and to elucidate the mechanisms underlying these fluxes; (3) to search for effects of lithium on membrane fluxes of compounds possibly related to mood disorders, such as neurotransmitters, metabolites, and their precursors; and (4) to determine which regions of the intestine are effective in absorbing lithium.